ArticleThe Journal of clinical investigation2023
Endogenous adenine mediates kidney injury in diabetic models and predicts diabetic kidney disease in patients.
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Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 2 of them syntheses that pooled it.
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48citing papers in PubMed, 2 pooled it
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Who cites it
48 citing papers in PubMed, 2 syntheses or guidelines pooled it, 56 citations in OpenAlex.
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- Mass spectrometry-based human spatial omics: fundamentals, innovations, and applications.Journal of biomedical science · 2026Pooled it
- AI-assisted metabolomic profiling identifies candidate metabolites associated with diabetic kidney disease staging in a Korean cohort.iScience · 2026Article
- Bibliometrics and visualization analysis: Big data research on diabetic kidney disease from 2000 to 2025.Medicine · 2026Article
- Nuclear Magnetic Resonance-Based Urinary Metabolic Profiling for Assessing Heat Stress-Related Incident Kidney Injury in Health-Care Workers.GeoHealth · 2026Article
- Research progress in single‑cell omics technologies for kidney disease (Review).International journal of molecular medicine · 2026Review
- Spatial metabolomics: A new tool for unravelling the metabolic disorders and heterogeneity in diabetic kidney disease (Review).International journal of molecular medicine · 2026Review
- Spatial metabolomics and multiomics integration for breakthroughs in precision medicine for kidney disease.Nature reviews. Nephrology · 2026Review
- Urinary biomarkers of diabetic kidney disease.World journal of diabetes · 2026Review
- Metabolic memory in diabetic complications: evidence for persistent cellular states and limits of therapeutic reversal.Frontiers in endocrinology · 2026Review
- From albuminuria to multi-omics signatures: emerging biomarkers and drug targets for early-stage chronic kidney disease.Frontiers in pharmacology · 2026Review
- Diagnostic value of tubular and glomerular biomarkers across different stages of kidney injury in patients with type 2 diabetic nephropathy.Frontiers in endocrinology · 2026Observational
- New Insights into the Role of Mitochondrial Dysfunction in Diabetic Kidney Disease in the Omics Era.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
- Urine as a source of biomarkers and biological knowledge in chronic kidney disease.Nature reviews. Nephrology · 2026Review
- Protection against cisplatin-induced acute kidney injury by hellgrammite extract: insights from comprehensive metabolomics.Frontiers in pharmacology · 2026Article
- Artesunate alleviates cisplatin-induced nephrotoxicity by regulating tryptophan metabolism and inhibiting ferroptosis.Frontiers in pharmacology · 2026Article
- Urinary metabolomics identifies isoleucine as a prognostic biomarker for progression of diabetic kidney disease.Frontiers in endocrinology · 2026Article
- Association of HDL2b with chronic kidney disease in type 2 diabetes mellitus populations.Frontiers in endocrinology · 2026Article
- Metabolomics of saliva, serum, and urine for pathogenesis, diagnosis, and prognosis in gestational diabetes mellitus.Nature communications · 2025Article
- Interconnection between myasthenia gravis and type 2 diabetes: emerging role of metformin in modulating PI3K/AKT/mTOR/AMPK axis.Metabolic brain disease · 2025Review
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Authors and funding
41 authors at 20 institutions in 9 countries.
Kumar SharmaCenter for Precision Medicine and.
Guanshi ZhangCenter for Precision Medicine and.
Jens HansenDepartment of Pharmacological Sciences and Institute for Systems Biomedicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Petter BjornstadDivision of Nephrology, Department of Medicine and Section of Endocrinology, Department of Pediatrics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Hak Joo LeeCenter for Precision Medicine and.
Rajasree MenonDepartment of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Leila HejaziCenter for Precision Medicine and.
Jian-Jun LiuClinical Research Unit, Khoo Teck Puat Hospital, Singapore.
Anthony FranzoneCenter for Precision Medicine and.
Helen C LookerChronic Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, Arizona, USA.
Byeong Yeob ChoiCenter for Precision Medicine and.
Roman FernandezDepartment of Population Health Sciences and.
Manjeri A VenkatachalamCenter for Precision Medicine and.
Luxcia KugathasanDepartment of Medicine, Division of Nephrology, University Health Network, Toronto, Ontario, Canada. Department of Physiology and Cardiovascular Sciences Collaborative Specialization, University of Toronto, Toronto, Canada.
Vikas S SridharDepartment of Medicine, Division of Nephrology, University Health Network, Toronto, Ontario, Canada. Department of Physiology and Cardiovascular Sciences Collaborative Specialization, University of Toronto, Toronto, Canada.
Loki NatarajanHerbert Wertheim School of Public Health and.
Jing ZhangMoores Cancer Center, University of California, San Diego, La Jolla, California, USA.
Varun S SharmaCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria.
Brian KwanDepartment of Health Science, California State University, Long Beach, Long Beach, California, USA.
Sushrut S WaikarSection of Nephrology, Department of Medicine, Boston Medical Center and Boston University, Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA.
Jonathan HimmelfarbDepartment of Medicine, Division of Nephrology, Kidney Research Institute, University of Washington, Seattle, Washington, USA.
Katherine R TuttleDepartment of Medicine, Division of Nephrology, Kidney Research Institute, University of Washington, Seattle, Washington, USA.
Bryan KestenbaumDepartment of Medicine, Division of Nephrology, Kidney Research Institute, University of Washington, Seattle, Washington, USA.
Tobias FuhrerInstitute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland.
Harold I FeldmanCenter for Clinical Epidemiology and Biostatistics and Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, USA.
Ian H de BoerDepartment of Medicine, Division of Nephrology, Kidney Research Institute, University of Washington, Seattle, Washington, USA.
Fabio C TucciEpigen Biosciences Inc., San Diego, California, USA.
John SedorCleveland Clinic, Cleveland, Ohio, USA.
Hiddo Lambers HeerspinkDepartment of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, Groningen, Netherlands.
Jennifer SchaubDepartment of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Edgar A OttoDepartment of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Jeffrey B HodginDepartment of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Matthias KretzlerDepartment of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA.
Christopher R AndertonCenter for Precision Medicine and.
Theodore AlexandrovStructural and Computational Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
David CherneyDepartment of Medicine, Division of Nephrology, University Health Network, Toronto, Ontario, Canada. Department of Physiology and Cardiovascular Sciences Collaborative Specialization, University of Toronto, Toronto, Canada.
Su Chi LimClinical Research Unit, Khoo Teck Puat Hospital, Singapore.
Robert G NelsonChronic Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, Arizona, USA.
Jonathan GelfondCenter for Precision Medicine and.
Ravi IyengarDepartment of Pharmacological Sciences and Institute for Systems Biomedicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Kidney Precision Medicine Project
The University of Texas Health Science Center at San Antonio · USUniversity of Michigan · USNorthwest Kidney Centers · USUniversity Health Network · CAIcahn School of Medicine at Mount Sinai · USNational Institute of Diabetes and Digestive and Kidney Diseases · USUC San Diego Health System · USAustrian Academy of Sciences · ATBoston University · USCleveland Clinic · USEpigen Biosciences (United States) · USETH Zurich · CHEuropean Molecular Biology Laboratory · DEKhoo Teck Puat Hospital · SGNational University of Singapore · SGPacific Northwest National Laboratory · USPatient-Centered Outcomes Research Institute · USUniversity Medical Center Groningen · NLUniversity of California, Los Angeles · USUniversity of Colorado Anschutz Medical Campus · US
Funding
OTA-21-015A Post-Acute Sequelae of SARS-CoV-2 Infection Initiative: NYU Langone Health Clinical Science Core, Data Resource Core, and PASC Biorepository CoreOT2HL161847 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI GROSS, RACHEL SHARON, HORWITZ, LEORA · 2021 to 2025
$651.0MUCSF CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTEUL1RR024131 · NCRR · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JOHNSTON, S. CLAIBORNE · 2006 to 2011
$111.2MTransform Dissemination and Implementation Science in CTSA ProgramsUL1TR002319 · NCATS · UNIVERSITY OF WASHINGTON · PI John K. Amory · 2017 to 2026
$100.0MScientific and Data Coordinating Center(SDCC) for the P*U01DK060990 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI FELDMAN, HAROLD I · 2001 to 2017
$50.1MClinical and Translational Science Collaborative of ClevelandUL1TR000439 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI KONSTAN, MICHAEL W. · 2012 to 2016
$50.0MMichigan Institute for Clinical and Health Research (MCHR)UL1TR000433 · NCATS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MASHOUR, GEORGE ALEXANDER · 2012 to 2016
$49.9MInstitutional Clinical and Translational Science AwardUL1TR000003 · NCATS · UNIVERSITY OF PENNSYLVANIA · PI FITZGERALD, GARRET A · 2012 to 2015
$38.9MClinical and Translational Science Collaborative of ClevelandUL1TR002548 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI MCCOMSEY, GRACE A · 2018 to 2022
$35.5MClinical and Translational Science Collaborative of Northern Ohio, Catalyzing Linkages to Equity in Health (CLE Health)UM1TR004528 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI GRACE A MCCOMSEY · 2023 to 2026
$32.1MTulane COBRE in Cardiometabolic Diseases Clinical Research CoreP20GM109036 · NIGMS · TULANE UNIVERSITY OF LOUISIANA · PI JING CHEN · 2016 to 2026
$25.3MUnited States Military HIV Research Program (MHRP) Clinical Trials UnitUM1AI108568 · NIAID · WALTER REED ARMY INSTITUTE OF RESEARCH · PI Julie A. Ake, Merlin L Robb · 2014 to 2026
$24.3MRegional Pilot And Feasibility Study Grants ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Mehboob A Hussain · 2013 to 2026
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Abstract
Diabetic kidney disease (DKD) can lead to end-stage kidney disease (ESKD) and mortality; however, few mechanistic biomarkers are available for high-risk patients, especially those without macroalbuminuria. Urine from participants with diabetes from the Chronic Renal Insufficiency Cohort (CRIC) study, the Singapore Study of Macro-angiopathy and Micro-vascular Reactivity in Type 2 Diabetes (SMART2D), and the American Indian Study determined whether urine adenine/creatinine ratio (UAdCR) could be a mechanistic biomarker for ESKD. ESKD and mortality were associated with the highest UAdCR tertile in the CRIC study and SMART2D. ESKD was associated with the highest UAdCR tertile in patients without macroalbuminuria in the CRIC study, SMART2D, and the American Indian study. Empagliflozin lowered UAdCR in nonmacroalbuminuric participants. Spatial metabolomics localized adenine to kidney pathology, and single-cell transcriptomics identified ribonucleoprotein biogenesis as a top pathway in proximal tubules of patients without macroalbuminuria, implicating mTOR. Adenine stimulated matrix in tubular cells via mTOR and stimulated mTOR in mouse kidneys. A specific inhibitor of adenine production was found to reduce kidney hypertrophy and kidney injury in diabetic mice. We propose that endogenous adenine may be a causative factor in DKD.
Indexed as
Diabetes Mellitus, ExperimentalDiabetes Mellitus, Type 2Diabetic NephropathiesKidney Failure, ChronicAdenineAnimalsBiomarkersHumansKidneyMiceTOR Serine-Threonine KinasesAdenineBiomarkersTOR Serine-Threonine KinasesChronic kidney diseaseDiabetesFibrosisNephrology
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